title: The galectin CvGal1 from the eastern oyster (Crassostrea virginica) binds to blood group A oligosaccharides on the hemocyte surface.
abstract: The galectin CvGal1 from the eastern oyster (Crassostrea virginica), which possesses four tandemly arrayed carbohydrate recognition domains, was previously shown to display stronger binding to galactosamine and N-acetylgalactosamine relative to d-galactose. CvGal1 expressed by phagocytic cells is "hijacked" by the parasite Perkinsus marinus to enter the host, where it proliferates and causes systemic infection and death. In this study, a detailed glycan array analysis revealed that CvGal1 preferentially recognizes type 2 blood group A oligosaccharides. Homology modeling of the protein and its oligosaccharide ligands supported this preference over type 1 blood group A and B oligosaccharides. The CvGal ligand models were further validated by binding, inhibition, and competitive binding studies of CvGal1 and ABH-specific monoclonal antibodies with intact and deglycosylated glycoproteins, hemocyte extracts, and intact hemocytes and by surface plasmon resonance analysis. A parallel glycomic study carried out on oyster hemocytes (Kurz, S., Jin, C., Hykollari, A., Gregorich, D., Giomarelli, B., Vasta, G. R., Wilson, I. B. H., and Paschinger, K. (2013) J. Biol. Chem. 288) determined the structures of oligosaccharides recognized by CvGal1. Proteomic analysis of the hemocyte glycoproteins identified β-integrin and dominin as CvGal1 "self"-ligands. Despite strong CvGal1 binding to P. marinus trophozoites, no binding of ABH blood group antibodies was observed. Thus, parasite glycans structurally distinct from the blood group A oligosaccharides on the hemocyte surface may function as potentially effective ligands for CvGal1. We hypothesize that carbohydrate-based mimicry resulting from the host/parasite co-evolution facilitates CvGal1-mediated cross-linking to β-integrin, located on the hemocyte surface, leading to cell activation, phagocytosis, and host infection.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202, USA.
authors.forename: Chiguang
authors.initials: C
authors.lastname: Feng
authors.forename: Anita
authors.initials: A
authors.lastname: Ghosh
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Amin
authors.forename: Barbara
authors.initials: B
authors.lastname: Giomarelli
authors.forename: Surekha
authors.initials: S
authors.lastname: Shridhar
authors.forename: Aditi
authors.initials: A
authors.lastname: Banerjee
authors.forename: José A
authors.initials: JA
authors.lastname: Fernández-Robledo
authors.forename: Mario A
authors.initials: MA
authors.lastname: Bianchet
authors.forename: Lai-Xi
authors.initials: LX
authors.lastname: Wang
authors.forename: Iain B H
authors.initials: IB
authors.lastname: Wilson
authors.forename: Gerardo R
authors.initials: GR
authors.lastname: Vasta
mesh_terms: D000017:ABO Blood-Group System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049896:Crassostrea / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000469:parasitology; D037161:Galectins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006434:Hemocytes / Q000737:chemistry* / Q000378:metabolism / Q000469:parasitology; D009844:Oligosaccharides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D040901:Proteomics / Q000379:methods
chemical_list: D000017:ABO Blood-Group System; D037161:Galectins; D009844:Oligosaccharides
keywords: Blood Group A Oligosaccharide; Galectin; Hemocyte; Molecular Docking; Oyster; Parasite; Perkinsus marinus; Phagocytosis; Surface Plasmon Resonance (SPR)